Journal article
Authors list: Holz, Meike Stefanie; Janning, Angela; Renne, Christoph; Gattenloehner, Stefan; Spieker, Tilmann; Braeuninger, Andreas
Publication year: 2013
Pages: 173-183
Journal: Molecular Cancer Therapeutics
Volume number: 12
Issue number: 2
ISSN: 1535-7163
eISSN: 1538-8514
Open access status: Green
DOI Link: https://doi.org/10.1158/1535-7163.MCT-12-0532
Publisher: American Association for Cancer Research
Abstract:
Hodgkin-Reed/Sternberg (HRS) cells of classical Hodgkin lymphoma show aberrant expression and activation of several receptor tyrosine kinases (RTK) in the majority of cases. Therefore, we tested whether tyrosine kinase inhibitors (TKI) already in clinical use or late stages of clinical trials have antiproliferative effects on HRS cell lines and evaluated the targets, affected signaling pathways, and mechanisms of cell death and resistance. Sorafenib and lestaurtinib had antiproliferative effects on HRS cell lines at concentrations achievable in patients. Sorafenib inhibited platelet-derived growth factor receptor (PDGFR) alpha, TRKA and RON, caused decreases in total and phosphorylated amounts of several signaling molecules, and provoked caspase-3-independent cell death, most likely due to endoplasmic reticulum stress as indicated by upregulation of GADD34 and GADD153 and phosphorylation of PERK. Lestaurtinib inhibited TRKA, PDGFR alpha, RON, and JAK2 and had only a cytostatic effect. Besides deactivation, lestaurtinib also caused activation of signaling pathways. It caused increases in CD30L and TRAIL expression, and CD30L/CD30 signaling likely led to the observed concomitant activation of extracellular signal-regulated kinase 1/2 and the alternative NF-kappa B pathway. These data disclose the possible use of sorafenib for the treatment of Hodgkin lymphoma and highlight NF-kappa B activation as a potential novel mechanism of resistance toward TKIs. Mol Cancer Ther; 12(2); 173-83. (C) 2012 AACR.
Citation Styles
Harvard Citation style: Holz, M., Janning, A., Renne, C., Gattenloehner, S., Spieker, T. and Braeuninger, A. (2013) Induction of Endoplasmic Reticulum Stress by Sorafenib and Activation of NF-κB by Lestaurtinib as a Novel Resistance Mechanism in Hodgkin Lymphoma Cell Lines, Molecular Cancer Therapeutics, 12(2), pp. 173-183. https://doi.org/10.1158/1535-7163.MCT-12-0532
APA Citation style: Holz, M., Janning, A., Renne, C., Gattenloehner, S., Spieker, T., & Braeuninger, A. (2013). Induction of Endoplasmic Reticulum Stress by Sorafenib and Activation of NF-κB by Lestaurtinib as a Novel Resistance Mechanism in Hodgkin Lymphoma Cell Lines. Molecular Cancer Therapeutics. 12(2), 173-183. https://doi.org/10.1158/1535-7163.MCT-12-0532
Keywords
ANTITUMOR-ACTIVITY; C-FLIP; PROTEIN-KINASE INHIBITORS; TYROSINE KINASES